This application is generally in the area of biocompatible polymeric materials which can be applied to biological and non-biological surfaces to minimize cell-cell interactions and adhesion of cells or tissue to the surfaces.
There is a need for materials, and methods of use thereof, which can be used to encapsulate cells and tissues or biologically active molecules which are biocompatible, and which do not elicit specific or non-specific immune responses. An important aspect of the use of these materials in vivo is that they must be applied within the time of a short surgical procedure or before the material to be encapsulated disperses, is damaged or dies.
It is often desirable to implant exogenous cells into a patient, for example, to produce various products the patient is incapable of preparing. An example of this is implantation of exogenous Islets of Langerhans cells to produce insulin in a diabetic patient. However, unless protected, exogenous cells are destroyed immediately following transplantation. Numerous attempts have been made to encapsulate the cells to minimize the body's efforts to destroy them.
Cells have been encapsulated using the ionic crosslinking of alginate (a polyanion) with polylysine or polyornithine (polycation) (Goosen, et al., Biotechnology and Bioengineering, 27:146 (1985)). This technique offers relatively mild encapsulating conditions. Microcapsules formed by the coacervation of alginate and poly(L-lysine) have been shown to be immunoprotective. However, the capsules do not remain intact long after implantation, or are quickly surrounded by fibrous tissue.
The biocompatibility of alginate-poly(L-lysine) microcapsules has been reported to be significantly enhanced by incorporating a graft copolymer of PLL and PEO on the microcapsule surface (Sawhney, et al., Biomaterials, 13, 863-870 (1991)). The PEO chain is highly water soluble and highly flexible. PEO chains have an extremely high motility in water and are essentially non-ionic in structure. Immobilization of PEO on a surface has been largely carried out by the synthesis of graft copolymers having PEO side chains.
U.S. Pat. Nos. 5,573,934 and 5,626,863 to Hubbell et al. disclose hydrogel materials including a water-soluble region such as polyethylene glycol and a biodegradable region, including various biodegradable polymers such as polylactide and polyglycolide, terminated with photopolymerizable groups such as acrylates. These materials can be applied to a tissue surface and polymerized, for example, to form tissue coatings. These materials are adhered to tissue surfaces by polymerizing the photopolymerizable groups on the materials after they have been applied to the tissue surface.
U.S. Pat. No. 5,627,233 to Hubbell et al. discloses multifunctional polymeric materials for use in inhibiting adhesion and immune recognition between cells and tissues. The materials include a tissue binding component (polycation) and a tissue non-binding component (polynonion). In particular, Hubbell discloses various PEG/PLL copolymers, with molecular weights greater than 300, with structures which include AB copolymers, ABA copolymers, and brush-type copolymers. These polymers are being commercially developed for use as tissue sealants and to prevent surgical adhesions.
It is therefore an object of the present invention to provide a polymeric material that can be applied to living cells and tissues, in a very short time period, to protect the cells and tissues from cell to cell interactions, such as adhesion.
It is a further object of the present invention to provide a polymeric material which is biocompatible and resistant to degradation for a specific time period.
It is a further object of the present invention to provide compositions for inhibiting tissue adhesion and cell-cell contact within the body, as well as methods for making and using the compositions.